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- W2046023917 abstract "Single-molecule force spectroscopy methods use optical traps or tiny cantilevers to impose controlled forces to individual molecules for studying their mechanical behavior and transitions along specific paths called reaction coordinates. A powerful application of these sophisticated approaches is the extraction of activation energy barriers and intrinsic rates of transition from measurements of the rupture force, i.e., when the molecules stretched at a speed undergoes sudden unfolding. Existing analyses of force measurements relies heavily on theoretical models for reliable extraction of kinetics and energetic properties. Despite significant advances, there remain large gaps in fully exploiting the experiments and their analyses. Specifically, the effect of pulling device stiffness or compliance has not been comprehensively captured. Hence, the best models for extracting molecular parameters can only be applied to measurements obtained from soft pulling devices (e.g., optical tweezers) and result in well-documented discrepancies when applied to stiff devices (e.g., AFM). This restriction makes pulling speed the only control parameter in the experiments, making reliable extraction of molecular properties problematic and prone to error. Here we present an analytical model derived from physical principles for extracting the intrinsic rates and activation free energies from rupture force measurements that is applicable to the entire range of pulling speeds and device stiffnesses. The model therefore is not restricted to the analyses of force measurements performed with soft pulling devices only. On the contrary, the model allows better design of experiments that specifically exploit device stiffness as a control parameter in addition to pulling speed for a more reliable estimation of energetic and kinetic parameters. The model also helps explain previous discrepancies noted in rupture forces measured with devices of different effective stiffnesses and provides a framework for modeling other stiffness-related issues in single-molecule force spectroscopy." @default.
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- W2046023917 date "2010-01-01" @default.
- W2046023917 modified "2023-09-27" @default.
- W2046023917 title "Model for Harnessing the Device Stiffness in Dynamic Single-Molecule Force Spectroscopy" @default.
- W2046023917 doi "https://doi.org/10.1016/j.bpj.2009.12.983" @default.
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